Prosthetic implant delivery device with introducer catheter

ABSTRACT

A delivery system and a method for deploying a cardiovascular prosthetic implant using a minimally invasive procedure are disclosed. The delivery system comprises an introducer catheter, a delivery catheter having a proximal end and a distal end, and a seal assembly, wherein an outer diameter of the distal end of the delivery catheter is greater than an inner diameter of the distal end of the introducer catheter.

PRIORITY CLAIM TO RELATED PROVISIONAL APPLICATIONS

This present application claims priority benefit under 35 U.S.C. §119(e)from U.S. Provisional Application No. 61/640,862, filed May 1, 2012,entitled “Prosthetic Implant Delivery Device with Introducer Catheter,”and U.S. Provisional Application No. 61/707,744, filed Sep. 28, 2012,entitled “Prosthetic Implant Delivery Device with Introducer Catheter,”which is incorporated by reference herein.

BACKGROUND

1. Field

The present invention relates to medical methods and devices, and, morespecifically, to methods and devices for percutaneously implanting avalve.

2. Description of the Related Art

The circulatory system is a closed loop bed of arterial and venousvessels supplying oxygen and nutrients to the body extremities throughcapillary beds. The driver of the system is the heart providing correctpressures to the circulatory system and regulating flow volumes as thebody demands. Deoxygenated blood enters heart first through the rightatrium and is allowed to the right ventricle through the tricuspidvalve. Once in the right ventricle, the heart delivers this bloodthrough the pulmonary valve and to the lungs for a gaseous exchange ofoxygen. The circulatory pressures carry this blood back to the heart viathe pulmonary veins and into the left atrium. Filling of the left atriumoccurs as the mitral valve opens allowing blood to be drawn into theleft ventricle for expulsion through the aortic valve and on to the bodyextremities. When the heart fails to continuously produce normal flowand pressures, a disease commonly referred to as heart failure occurs.

The four valves of the heart (i.e., the tricuspid, the pulmonary valve,the mitral valve and the aortic valve) function to ensure that bloodflows in only one direction through the heart. The valves are made ofthin flaps of tissue that open and close as the heart contracts.Valvular heart disease is any disease process involving one or more ofthe valves of the heart. For example, disease and age can cause thetissue of a heart valve to thicken and harden, which can case the valveto fail to open properly and interfere with blood flow. This thickeningprocess is often called stenosis. A heart valve can also become weakenedor stretched such it no longer closes properly, which can cause bloodleak back through the valve. This leakage through the valve is oftencalled regurgitation. Problems with a heart valve can increase theamount of work performed by the heart. The increase in work can causethe heart muscle to enlarge or thicken to make up for the extraworkload.

The standard treatment for replacing an improperly working valve is toreplace it. Traditionally, valve replacement has been accomplished viaan open surgical procedure. More recently, transcatheter valvereplacement has been attempted via percutaneous method such as acatheterization or delivery mechanism utilizing the vasculaturepathways. Open surgical procedures often include the sewing of a newvalve to the existing tissue structure for securement. Access to thesesites generally include a thoracotomy or a sternotomy for the patientand include a great deal of recovery time. Such open-heart surgicalprocedures can include placing the patient on heart bypass to continueblood flow to vital organs such as the brain during the surgery.Although open heart surgical valve repair and replacement cansuccessfully treat many patients with valvular insufficiency, techniquescurrently in use are attended by significant morbidity and mortality dueto the inherent invasiveness of open heart surgery.

According to recent estimates, more than 79,000 patients are diagnosedwith aortic and mitral valve disease in U.S. hospitals each year. Morethan 49,000 mitral valve or aortic valve replacement procedures areperformed annually in the U.S., along with a significant number of heartvalve repair procedures. Since surgical techniques are highly invasive,the need for a less invasive method of heart valve replacement has longbeen recognized. As noted above, transcatheter heart valve systems haverecently been developed in which heart valves are delivered through theheart by an intravascular catheter. Such transcatheter heart valves havethe potential to reduce the anticipated mortality and morbidity ratesassociated with traditional surgical valve surgery particularly amongpatients of advanced age and/or with comorbidities. However, a needremains for improvements over the basic concept of transcatheter heartvalve replacement. For example, current transcatheter valve replacementcan sometimes result in vascular complications such as aorticdissection, access site or access related vascular and/or distalembolization from a vascular source. One method for reducing suchcomplications is to reduce ratio of the diameter of the delivery devicefor the heart valve.

SUMMARY

One arrangement for delivering a cardiovascular prosthetic implant usinga minimally invasive procedure comprises an introducer catheter having aproximal end and a distal end. A delivery catheter extends through theintroducer catheter. The delivery catheter has a proximal end and adistal end extending beyond the distal end of the introducer catheter. Ahemostasis seal assembly can be positioned a proximal end of theintroducer catheter. An outer diameter of the distal end of the deliverycatheter is greater than an inner diameter of the distal end of theintroducer catheter.

In the above mentioned arrangement, the delivery system can include acardiovascular prosthetic implant at the distal end of the deliverycatheter. The cardiovascular prosthetic implant can include aninflatable cuff and a tissue valve.

In any of the above mentioned arrangements, the delivery system caninclude at least one link between the catheter body and thecardiovascular prosthetic implant.

In any of the above mentioned arrangements, the inner diameter of thedistal end of the introducer can be 16 F or less.

In any of the above mentioned arrangements, the introducer catheter caninclude an elongated tapered tip.

In any of the above mentioned arrangements, the introducer catheter caninclude a tapered tip that can transition from a first enlarged lengthconfiguration to a second shorter configuration.

In any of the above mentioned arrangements, the system can include along tip in a first configuration and a short tip in a secondconfiguration.

In any of the above mentioned arrangements, the system can include a tipthat has a straight configuration and a bent configuration.

In another arrangement, a delivery system for delivering acardiovascular prosthetic implant using a minimally invasive procedureincludes an introducer catheter having a proximal end and a distal endand a lumen extending from the proximal end to the distal end of theintroducer catheter. The introducer catheter has an outer diameterdefined by an outer surface of the introducer catheter and an innerdiameter defining the through lumen. A delivery catheter extends throughthe introducer catheter. The delivery catheter comprises a tubular bodyhaving a proximal end and a distal end. The distal end includes a sheathjacket and stem portion extending proximally from the sheath jacket. Thesheath jacket has an outer surface that defines an outer diameter of thesheath jacket. The outer diameter of the sheath jacket is greater thanthe inner diameter of the introduced catheter at the distal end of theintroducer catheter. The stem portion has an outer surface that definesan outer diameter of the stem portion. The outer diameter of the stemportion is smaller than the inner diameter of the introducer catheter. Acardiovascular prosthetic implant is positioned at least partiallywithin the sheath jacket.

In any of the above mentioned arrangements, the delivery system caninclude a seal assembly at a proximal end of the introducer catheter.

In any of the above mentioned arrangements, the delivery system caninclude a cardiovascular prosthetic implant having an inflatable cuffand a tissue valve.

In any of the above mentioned arrangements, the delivery system caninclude at least one inflation lumen extending between an inflatablecuff and the proximal end of the introducer catheter, the inflationlumen extending through the delivery catheter.

In any of the above mentioned arrangements, the delivery system caninclude at least one link between the catheter body and a cardiovascularprosthetic implant.

In any of the above mentioned arrangements, the inner diameter of thedistal end of the introducer catheter is about 16 F.

In any of the above mentioned arrangements, the delivery system caninclude a tubing extending through the delivery catheter and acardiovascular prosthetic implant.

In any of the above mentioned arrangements, the delivery system caninclude a distal tip coupled to a distal end of the tubing, the distaltip having a maximum outside diameter that is approximately the same asthe outside diameter of a jacket sheath.

In any of the above mentioned arrangements, the delivery system caninclude a sheath jacket is coupled to a distal end of a stem portion.

In another arrangement, a prosthetic implant is positioned within aheart. The method comprises advancing an introducer catheter positionedover a delivery catheter comprising a prosthetic valve into a patient'svascular system, translumenally advancing the prosthetic valve to aposition proximate a native valve of the heart; and deploying theprosthetic valve.

In the above mentioned method, the method can include advancing theintroducer catheter and delivery catheter over a guidewire.

In any of the above mentioned methods, the method can include insertingthe introducer catheter into the femoral artery.

In any of the above mentioned methods, the method can include advancingthe prosthetic valve through the aorta.

In any of the above mentioned methods, the method can include inflatinga portion of the prosthetic valve.

In any of the above mentioned methods, the method can include insertinga distal end of the delivery catheter directly into an access vessel.

In any of the above mentioned methods, the method can include removingthe delivery catheter and introducer catheter together from the patient.

Further features and advantages of the present invention will becomeapparent from the detailed description of preferred embodiments whichfollows, when considered together with the attached drawings and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional schematic view of a heart and its majorblood vessels.

FIG. 2A is a partial cut-away view a left ventricle and aortic with anprosthetic aortic valve implant according to one embodiment.

FIG. 2B is a side view of the implant of FIG. 2A positioned across anative aortic valve.

FIG. 3A is a front perspective view of the implant of FIG. 2B.

FIG. 3B is a front perspective view of an inflatable support structureof the implant of FIG. 3A.

FIG. 3C is a cross-sectional side view of the implant of FIG. 3A.

FIG. 3D is an enlarged cross-sectional view of an upper portion of FIG.3C.

FIG. 4 is a cross-sectional view of the connection port and theinflation valve in the implant of FIG. 3B.

FIG. 5A is a side perspective view of a deployment catheter withretracted implant.

FIG. 5B is a side perspective view of the deployment catheter of FIG. 5Awith the implant outside of the outer sheath jacket.

FIG. 5C is a side perspective view of the position-and-fill lumen (PFL),which is a component of the deployment catheter of FIGS. 5A and 5B.

FIG. 6 is a cross-sectional view taken through line A-A of FIG. 5B.

FIG. 7 is a side perspective view of a loading tool base.

FIG. 8A is a side perspective view of an introduced catheter deploymentcatheter with retracted implant.

FIG. 8B is a side perspective view of the introducer catheter anddeployment catheter of FIG. 8A with the implant outside of the outersheath jacket.

FIG. 8C is a side perspective view of the position-and-fill lumen (PFL),which is a component of the deployment catheter of FIGS. 8A and 8B.

FIG. 9 is a side view of the introducer catheter of FIGS. 8A-8C.

FIG. 10A is a side view of the deployment catheter of FIGS. 8A-8C.

FIG. 10B is an exploded view of a seal assembly.

FIG. 11A illustrates a step of partially deploying and positioning anartificial valve implant.

FIG. 11B illustrates a second step of partially deploying andpositioning an artificial valve implant.

FIG. 11C illustrates a third step of partially deploying and positioningan artificial valve implant.

FIG. 12A illustrates a step deploying, testing and repositioning anartificial valve implant.

FIG. 12B illustrates a step deploying, testing and repositioning anartificial valve implant.

FIG. 12C illustrates a step deploying, testing and repositioning anartificial valve implant.

FIG. 12D illustrates a step deploying, testing and repositioning anartificial valve implant.

FIG. 12E illustrates a step deploying, testing and repositioning anartificial valve implant.

FIG. 13 illustrates a side view of another embodiment of a deploymentsystem.

FIG. 14 illustrates a side view of another embodiment of a deploymentsystem.

DETAILED DESCRIPTION

FIG. 1 is a schematic cross-sectional illustration of the anatomicalstructure and major blood vessels of a heart 10. Deoxygenated blood isdelivered to the right atrium 12 of the heart 10 by the superior andinferior vena cava 14, 16. Blood in the right atrium 12 is allowed intothe right ventricle 18 through the tricuspid valve 20. Once in the rightventricle 18, the heart 10 delivers this blood through the pulmonaryvalve 22 to the pulmonary arteries 24 and to the lungs for a gaseousexchange of oxygen. The circulatory pressures carry this blood back tothe heart via the pulmonary veins 26 and into the left atrium 28.Filling of the left atrium 28 occurs as the mitral valve 30 opensallowing blood to be drawn into the left ventricle 32 for expulsionthrough the aortic valve 34 and on to the body extremities through theaorta 36. When the heart 10 fails to continuously produce normal flowand pressures, a disease commonly referred to as heart failure occurs.

One cause of heart failure is failure or malfunction of one or more ofthe valves of the heart 10. For example, the aortic valve 34 canmalfunction for several reasons. For example, the aortic valve 34 may beabnormal from birth (e.g., bicuspid, calcification, congenital aorticvalve disease), or it could become diseased with age (e.g., acquiredaortic valve disease). In such situations, it can be desirable toreplace the abnormal or diseased valve 34.

FIG. 2 is a schematic illustration of the left ventricle 32, whichdelivers blood to the aorta 36 through the aortic valve 34. The aorta 36comprises (i) the ascending aorta 38, which arises from the leftventricle 32 of the heart 10, (ii) the aortic arch 10, which arches fromthe ascending aorta 38 and (iii) the descending aorta 42 which descendsfrom the aortic arch 40 towards the abdominal aorta (not shown). Alsoshown are the principal branches of the aorta 14, which include theinnomate artery 44 that immediately divides into the right carotidartery (not shown) and the right subclavian artery (not shown), the leftcarotid 46 and the subclavian artery 48.

Inflatable Prosthetic Aortic Valve Implant

With continued reference to FIG. 2A, a cardiovascular prosthetic implant800 in accordance with one embodiment is shown spanning the nativeabnormal or diseased aortic valve 34. The implant 800 and variousmodified embodiments thereof will be described in detail below. As willbe explained in more detail below, the implant 800 can be deliveredminimally invasively using an intravascular delivery catheter 900 ortrans apical approach with a trocar. Further details, additionalembodiments of and/or modifications of the implant or delivery systemcan be found in U.S. Pat. Nos. 7,641,686, 8,012,201 and U.S. PublicationNos. 2007/0005133; 2009/0088836 and 2012/0016468, the entirety of thesepatents and publications are hereby incorporated by reference herein intheir entirety.

The description below will be primarily in the context of replacing orrepairing an abnormal or diseased aortic valve 34. However, variousfeatures and aspects of methods and structures disclosed herein areapplicable to replacing or repairing the mitral 30, pulmonary 22 and/ortricuspid 20 valves of the heart 10 as those of skill in the art willappreciate in light of the disclosure herein. In addition, those ofskill in the art will also recognize that various features and aspectsof the methods and structures disclosed herein can be used in otherparts of the body that include valves or can benefit from the additionof a valve, such as, for example, the esophagus, stomach, ureter and/orvesicle, biliary ducts, the lymphatic system and in the intestines.

In addition, various components of the implant and its delivery systemwill be described with reference to coordinate system comprising“distal” and “proximal” directions. In this application, distal andproximal directions refer to the deployment system 900, which is used todeliver the implant 800 and advanced through the aorta 36 in a directionopposite to the normal direction of blood through the aorta 36. Thus, ingeneral, distal means closer to the heart while proximal means furtherfrom the heart with respect to the circulatory system.

In some embodiments, the implant 800 can be a prosthetic aortic valveimplant. With reference to FIG. 2B in the illustrated embodiment, theimplant 800 can have a shape that can be viewed as a tubular member orhyperboloid shape where a waist 805 excludes the native valve 34 orvessel and proximally the proximal end 803 forms a hoop or ring to sealblood flow from re-entering the left ventricle 32. Distally, the distalend 804 can also form a hoop or ring to seal blood from forward flowthrough the outflow track. Between the two ends 803 and 804, a valve 104can be mounted to the cuff or body 802 such that when inflated theimplant 800 excludes the native valve 34 or extends over the formerlocation of the native valve 34 and replaces its function. The distalend 804 can have an appropriate size and shape so that it does notinterfere with the proper function of the mitral valve, but stillsecures the valve adequately. For example, there can be a notch, recessor cut out in the distal end 804 of the device to prevent mitral valveinterference. The proximal end 803 can be designed to sit in the aorticroot. In one arrangement, the proximal end 803 can be shaped in such away that it maintains good apposition with the wall of the aortic root.This can prevent the device from migrating back into the ventricle 32.In some embodiments, the implant 800 can be configured such that it doesnot extend so high that it interferes with the coronary arteries.

Any number of additional inflatable rings or struts can be disposedbetween the proximal end 803 and distal end 804. The distal end 804 ofthe implant 800 can be positioned within the left ventricle 34 and canutilize the aortic root for axial stabilization as it may have a largerdiameter than the aortic lumen. This arrangement may lessen the need forhooks, barbs or an interference fit to the vessel wall. Since theimplant 800 can be placed without the aid of a dilatation balloon forradial expansion, the aortic valve 34 and vessel may not have anyduration of obstruction and would provide the patient with more comfortand the physician more time to properly place the device accurately.Since in the illustrated arrangement, the implant 800 is not utilizing asupport member with a single placement option as a plasticallydeformable or shaped memory metal stent does, the implant 800 can bemovable and or removable if desired. This could be performed multipletimes until the implant 800 is permanently disconnected from thedelivery catheter 900 as will be explained in more detail below. Inaddition, as will be described below, the implant 800 can includefeatures, which allow the implant 800 to be tested for proper function,sealing and sizing, before the catheter 900 is disconnected.

With reference to FIG. 3A, the implant 800 of the illustrated embodimentgenerally comprises the inflatable cuff or body 802, which is configuredto support the valve 104 (see FIG. 2A) that is coupled to the cuff 802.In some embodiments, the valve 104 is a tissue valve. In someembodiments, the tissue valve has a thickness equal to or greater thanabout 0.011 inches. In another embodiment, the tissue valve has athickness equal to or greater than about 0.018 inches. As will beexplained in more detail below, the valve 104 can be configured to movein response to the hemodynamic movement of the blood pumped by the heart10 between an “open” configuration where blood can throw the implant 800in a first direction and a “closed” configuration whereby blood isprevented from back flowing through the valve 104 in a second direction.

In the illustrated embodiment, the cuff 802 can comprise a thin flexibletubular material such as a flexible fabric or thin membrane with littledimensional integrity. As will be explained in more detail below, thecuff 802 can be changed preferably, in situ, to a support structure towhich other components (e.g., the valve 104) of the implant 800 can besecured and where tissue ingrowth can occur. Uninflated, the cuff 802can be incapable of providing support. In one embodiment, the cuff 802comprises Dacron, PTFE, ePTFE, TFE or polyester fabric as seen inconventional devices such as surgical stented or stent less valves andannuloplasty rings. The fabric thickness can range from about 0.002inches to about 0.020 inches depending upon material selection andweave. Weave density may also be adjusted from a very tight weave toprevent blood from penetrating through the fabric to a looser weave toallow tissue to grow and surround the fabric completely. In certainembodiments, the fabric may have a linear mass density about 20 denieror lower.

With reference to FIGS. 3B-3D, in the illustrated embodiment, theimplant 800 can include an inflatable structure 813 that is formed byone or more inflation channels 808. The inflatable channels 808 can beformed by a pair of distinct balloon rings or toroids (807 a and 807 b)and struts 806. In the illustrated embodiment, the implant 800 caninclude a proximal toroid 807 a at the proximal end 803 of the cuff 802and a distal toroid 807 b at the distal end 804 of the cuff 802. Thetoroids 807 can be secured to the cuff 802 in any of a variety ofmanners. With reference to FIGS. 3C and 3D, in the illustratedembodiment, the toroids 807 can be secured within folds 801 formed atthe proximal end 803 and the distal end 804 of the cuff 802. The folds801, in turn, can be secured by sutures or stitches 812. When inflated,the implant 800 can be supported in part by series of struts 806surrounding the cuff 802. In some embodiments, the struts 806 areconfigured so that the portions on the cuff run substantiallyperpendicular to the toroids. The struts can be sewn onto the cuff 802or can be enclosed in lumens made from the cuff material and swan ontothe cuff 802. The toroids 807 and the struts 806 together can form oneor more inflatable channels 808 that can be inflated by air, liquid orinflation media.

With reference to FIG. 3B, the inflation channels can be configured sothat the cross-sectional profile of the implant 800 is reduced when itis compressed or in the retracted state. For example, the inflationchannels 808 can be arranged in a step-function pattern. The inflationchannels 808 can have three connection ports 809 for coupling to thedelivery catheter 900 via position and fill lumen tubing (PFL) tubing916 (see FIGS. 5A-5C). In some embodiments, at least two of theconnection ports 809 also function as inflation ports, and inflationmedia, air or liquid can be introduced into the inflation channel 808through these ports. The PFL tubing 916 can be connected to theconnection ports 809 via suitable connection mechanisms. In oneembodiment, the connection between the PFL tubing 916 and the connectionport 809 is a screw connection. In some embodiments, an inflation valve810 is present in the connection port 809 and can stop the inflationmedia, air or liquid from escaping the inflation channels 808 after thePFL tubing is disconnected. In some embodiments, the distal toroid 807 band the proximal toroid 807 a can be inflated independently. In someembodiments, the distal toroid 807 b can be inflated separately from thestruts 806 and the proximal toroid 807 a. The separate inflation can beuseful during the positioning of the implant at the implantation site.With reference to FIGS. 3C and 3D, the portion of struts 806 can runparallel to the toroids 807 and can be encapsulated within the folds 801of the implant 800. This arrangement may also aid in reducing thecross-sectional profile when the implant is compressed or folded.

As mentioned above, the inflatable rings or toroids 807 and struts 806can form the inflatable structure 813, which, in turn, defines theinflation channels 808. The inflation channels 808 can receive inflationmedia to generally inflate the inflatable structure 813. When inflated,the inflatable rings 807 and struts 806 can provide structural supportto the inflatable implant 800 and/or help to secure the implant 800 thinthe heart 10. Uninflated, the implant 800 is a generally thin, flexibleshapeless assembly that is preferably incapable of support and isadvantageously able to take a small, reduced profile form in which itcan be percutaneously inserted into the body. As will be explained inmore detail below, in modified embodiments, the inflatable structure 813can comprise any of a variety of configurations of inflation channels808 that can be formed from other inflatable members in addition to orin the alternative to the inflatable rings 807 and struts 806 shown inFIGS. 3A and 3B. In one embodiment, the valve has an expanded diameterthat is greater than or equal to 22 millimeters and a maximum compresseddiameter that is less than or equal to 6 millimeters (18 F).

With particular reference to FIG. 3B, in the illustrated embodiment, thedistal ring 807 b and struts 806 can be joined such that the inflationchannel 808 of the distal ring 807 b is in fluid communication with theinflation channel 808 of some of the struts 806. The inflation channel808 of the proximal ring 807 a can also be in communication with theinflation channels 808 of the proximal ring 807 a and a few of thestruts 806. In this manner, the inflation channels of the (i) proximalring 807 a and a few struts 806 can be inflated independently from the(ii) distal ring 807 b and some struts. In some embodiments, theinflation channel of the proximal ring 807 a can be in communicationwith the inflation channel of the struts 806, while the inflationchannel of the distal ring 807 b is not in communication with theinflation channel of the struts. As will be explained in more detailbelow, the two groups of inflation channels 808 can be connected toindependent PFL tubing 916 to facilitate the independent inflation. Itshould be appreciated that in modified embodiments the inflatablestructure can include less (i.e., one common inflation channel) or moreindependent inflation channels. For example, in one embodiment, theinflation channels of the proximal ring 807 a, struts 806 and distalring 807 b can all be in fluid communication with each other such thatthey can be inflated from a single inflation device. In anotherembodiment, the inflation channels of the proximal ring 807 a, struts806 and distal ring 807 b can all be separated and therefore utilizethree inflation devices.

With reference to FIG. 3B, in the illustrated embodiment, each of theproximal ring 807 a and the distal ring 807 b can have a cross-sectionaldiameter of about 0.090 inches. The struts can have a cross-sectionaldiameter of about 0.060 inches. In some embodiments, within theinflation channels 808 are also housed valve systems that allow forpressurization without leakage or passage of fluid in a singledirection. In the illustrated embodiment shown in FIG. 3B, two endvalves or inflation valves 810 can reside at each end section of theinflation channels 808 adjacent to the connection ports 809. These endvalves 810 are utilized to fill and exchange fluids such as saline,contrast agent and inflation media. The length of this inflation channel808 can vary depending upon the size of the implant 800 and thecomplexity of the geometry. The inflation channel material can be blownusing heat and pressure from materials such as nylon, polyethylene,Pebax, polypropylene or other common materials that will maintainpressurization. The fluids that are introduced are used to create thesupport structure, where without them, the implant 800 can be anundefined fabric and tissue assembly. In one embodiment the inflationchannels 808 are first filled with saline and contrast agent forradiopaque visualization under fluoroscopy. This can make positioningthe implant 800 at the implantation site easier. This fluid isintroduced from the proximal end of the catheter 900 with the aid of aninflation device such as an endoflator or other devices to pressurizefluid in a controlled manner. This fluid can be transferred from theproximal end of the catheter 900 through the PFL tubes 916 which areconnected to the implant 800 at the end of each inflation channel 808 atthe connection port 809.

With reference to FIG. 3B, in the illustrated embodiment, the inflationchannel 808 can have an end valve 810 (i.e., inflation valve) at eachend whereby they can be separated from the PFL tubes 916 thusdisconnecting the catheter from the implant. This connection can be ascrew or threaded connection, a colleting system, an interference fit orother devices and methods of reliable securement between the twocomponents (i.e., the end valve 810 and the PFL tubes 916). In betweenthe ends of the inflation channel 808 can be an additional directionalvalve 811 to allow fluid to pass in a single direction. This allows forthe filling of each end of the inflation channel 808 and displacement offluid in a single direction. Once the implant 808 is placed at thedesired position while inflated with saline and contrast agent, thisfluid can be displaced by an inflation media that can solidify orharden. As the inflation media can be introduced from the proximal endof the catheter 900, the fluid containing saline and contrast agent ispushed out from one end of the inflation channel 808. Once the inflationmedia completely displaces the first fluid, the PFL tubes can then bedisconnected from the implant 800 while the implant 800 remains inflatedand pressurized. The pressure can be maintained in the implant 800 bythe integral valve (i.e., end valve 810) at each end of the inflationchannel 808. In the illustrated embodiment, this end valve 810 can havea ball 303 and seat to allow for fluid to pass when connected and sealwhen disconnected. In some case the implant 800 has three or moreconnection ports 809, but only two have inflation valves 810 attached.The connection port without the end valve 810 can use the sameattachment device such as a screw or threaded element. Since, theillustrated embodiment, this connection port is not used forcommunication with the support structure 813 and its filling, noinflation valve 810 is necessary. In other embodiments, all threeconnection ports 809 can have inflation valves 810 for introducingfluids or inflation media.

With reference to FIG. 4, the end valve system 810 can comprise atubular section 312 with a soft seal 304 and spherical ball 303 tocreate a sealing mechanism 313. The tubular section 312 in oneembodiment is about 0.5 cm to about 2 cm in length and has an outerdiameter of about 0.010 inches to about 0.090 inches with a wallthickness of about 0.005 inches to about 0.040 inches. The material caninclude a host of polymers such as nylon, polyethylene, Pebax,polypropylene or other common materials such as stainless steel, Nitinolor other metallic materials used in medical devices. The soft sealmaterial can be introduced as a liquid silicone or other material wherea curing occurs thus allowing for a through hole to be constructed bycoring or blanking a central lumen through the seal material. The softseal 304 can be adhered to the inner diameter of the wall of the tubularmember 312 with a through hole for fluid flow. The spherical ball 303can move within the inner diameter of the tubular member 312 where itseats at one end sealing pressure within the inflation channels and ismoved the other direction with the introduction of the PFL tube 916 butnot allowed to migrate too far as a stop ring or ball stopper 305retains the spherical ball 303 from moving into the inflation channel808. As the PFL tube 916 is screwed into the connection port 809, thespherical ball 303 is moved into an open position to allow for fluidcommunication between the inflation channel 808 and the PFL tube 916.When disconnected, the ball 303 ca move against the soft seal 304 andhalt any fluid communication external to the inflation channel 808leaving the implant 800 pressurized. Additional embodiments can utilizea spring mechanism to return the ball to a sealed position and othershapes of sealing devices may be used rather than a spherical ball. Aduck-bill style sealing mechanism or flap valve can also be used to haltfluid leakage and provide a closed system to the implant. Additional endvalve systems have been described in U.S. Patent Publication No.2009/0088836 to Bishop et al., which is thereby incorporated byreference herein.

The implant 800 of the illustrated embodiment ca allow delivery aprosthetic valve via catheterization in a lower profile and a safermanner than currently available. When the implant 800 is delivered tothe site via a delivery catheter 900, the implant 800 is a thin,generally shapeless assembly in need of structure and definition. At theimplantation site, the inflation media (e.g., a fluid or gas) can beadded via PFL tubes of the delivery catheter 900 to the inflationchannels 808 providing structure and definition to the implant 800. Theinflation media therefore can comprise part of the support structure forimplant 800 after it is inflated. The inflation media that is insertedinto the inflation channels 808 can be pressurized and/or can solidifyin situ to provide structure to the implant 800. Additional details andembodiments of the implant 800, can be found in U.S. Pat. No. 5,554,185to Block and U.S. Patent Publication No. 2006/0088836 to Bishop et al.,the disclosures of which are expressly incorporated by reference intheir entirety herein.

The cuff 802 can be made from many different materials such as Dacron,TFE, PTFE, ePTFE, woven metal fabrics, braided structures, or othergenerally accepted implantable materials. These materials may also becast, extruded, or seamed together using heat, direct or indirect,sintering techniques, laser energy sources, ultrasound techniques,molding or thermoforming technologies. Since the inflation channels 808generally surrounds the cuff 802, and the inflation channels 808 can beformed by separate members (e.g., balloons and struts), the attachmentor encapsulation of these inflation channels 808 can be in intimatecontact with the cuff material. In some embodiments, the inflationchannels 808 are encapsulated in the folds 801 or lumens made from thecuff material sewn to the cuff 802. These inflation channels 808 canalso be formed by sealing the cuff material to create an integral lumenfrom the cuff 802 itself. For example, by adding a material such as asilicone layer to a porous material such as Dacron, the fabric canresist fluid penetration or hold pressures if sealed. Materials can alsobe added to the sheet or cylinder material to create a fluid-tightbarrier.

Various shapes of the cuff 802 can be manufactured to best fitanatomical variations from person to person. As described above, thesemay include a simple cylinder, a hyperboloid, a device with a largerdiameter in its mid portion and a smaller diameter at one or both ends,a funnel type configuration or other conforming shape to nativeanatomies. The shape of the implant 800 is preferably contoured toengage a feature of the native anatomy in such a way as to prevent themigration of the device in a proximal or distal direction. In oneembodiment the feature that the device engages is the aortic root oraortic bulb 34 (see e.g., FIG. 2A), or the sinuses of the coronaryarteries. In another embodiment the feature that the device engages isthe native valve annulus, the native valve or a portion of the nativevalve. In certain embodiments, the feature that the implant 800 engagesto prevent migration has a diameter difference between 1% and 10%. Inanother embodiment, the feature that the implant 800 engages to preventmigration the diameter difference is between 5% and 40%. In certainembodiments the diameter difference is defined by the free shape of theimplant 800. In another embodiment the diameter difference preventsmigration in only one direction. In another embodiment, the diameterdifference prevents migration in two directions, for example proximaland distal or retrograde and antigrade. Similar to surgical valves, theimplant 800 will vary in diameter ranging from about 14 mm to about 30mm and have a height ranging from about 10 mm to about 30 mm in theportion of the implant 800 where the leaflets of the valve 104 aremounted. Portions of the implant 800 intended for placement in theaortic root can have larger diameters preferably ranging from about 20mm to about 45 mm. In some embodiment, the implant 800 can have anoutside diameter greater than about 22 mm when fully inflated.

In certain embodiments, the cuffs, inflated structure can conform (atleast partially) to the anatomy of the patient as the implant 800 isinflated. Such an arrangement may provide a better seal between thepatient's anatomy and the implant 800.

Different diameters of prosthetic valves may be needed to replace nativevalves of various sizes. For different locations in the anatomy,different lengths of prosthetic valves or anchoring devices will also berequired. For example a valve designed to replace the native aorticvalve needs to have a relatively short length because of the location ofthe coronary artery ostium (left and right arteries). A valve designedto replace or supplement a pulmonary valve could have significantlygreater length because the anatomy of the pulmonary artery allows foradditional length. Different anchoring mechanisms that may be useful foranchoring the implant 800 have been described in U.S. Patent PublicationNo. 2009/0088836 to Bishop et al.

In the embodiments described herein, the inflation channels 808 can beconfigured such that they are of round, oval, square, rectangular orparabolic shape in cross section. Round cross sections may vary fromabout 0.020-about 0.100 inches in diameter with wall thicknesses rangingfrom about 0.0005-about 0.010 inches. Oval cross sections may have anaspect ratio of two or three to one depending upon the desired cuffthickness and strength desired. In embodiments in which the inflationchannels 808 are formed by balloons, these channels 808 can beconstructed from conventional balloon materials such as nylon,polyethylene, PEEK, silicone or other generally accepted medical devicematerial

In some embodiments, portions of the cuff or body 802 can beradio-opaque to aid in visualizing the position and orientation of theimplant 800. Markers made from platinum gold or tantalum or otherappropriate materials may be used. These may be used to identifycritical areas of the valve that must be positioned appropriately, forexample the valve commissures may need to be positioned appropriatelyrelative to the coronary arteries for an aortic valve. Additionallyduring the procedure it may be advantageous to catheterize the coronaryarteries using radio-opaque tipped guide catheters so that the ostiumcan be visualized. Special catheters could be developed with increasedradio-opacity or larger than standard perfusion holes. The catheterscould also have a reduced diameter in their proximal section allowingthem to be introduced with the valve deployment catheter.

As mentioned above, during delivery, the body 802 can be limp andflexible providing a compact shape to fit inside a delivery sheath. Thebody 802 is therefore preferably made form a thin, flexible materialthat is biocompatible and may aid in tissue growth at the interface withthe native tissue. A few examples of material may be Dacron, ePTFE,PTFE, TFE, woven material such as stainless steel, platinum, MP35N,polyester or other implantable metal or polymer. As mentioned above withreference to FIG. 2A, the body 802 may have a tubular or hyperboloidshape to allow for the native valve to be excluded beneath the wall ofthe cuff 802. Within this cuff 802 the inflation channels 808 can beconnected to a catheter lumen for the delivery of an inflation media todefine and add structure to the implant 800. The valve 104, which isconfigured such that a fluid, such as blood, may be allowed to flow in asingle direction or limit flow in one or both directions, is positionedwithin the cuff 802. The attachment method of the valve 104 to the cuff802 can be by conventional sewing, gluing, welding, interference orother devices and methods generally accepted by industry.

In one embodiment, the cuff 802 would have a diameter of between about15 mm and about 30 mm and a length of between about 6 mm and about 70mm. The wall thickness would have an ideal range from about 0.01 mm toabout 2 mm. As described above, the cuff 802 may gain longitudinalsupport in situ from members formed by inflation channels or formed bypolymer or solid structural elements providing axial separation. Theinner diameter of the cuff 802 may have a fixed dimension providing aconstant size for valve attachment and a predictable valve open andclosure function. Portions of the outer surface of the cuff 802 mayoptionally be compliant and allow the implant 800 to achieveinterference fit with the native anatomy.

The implant 800 can have various overall shapes (e.g., an hourglassshape to hold the device in position around the valve annulus, or thedevice may have a different shape to hold the device in position inanother portion of the native anatomy, such as the aortic root).Regardless of the overall shape of the implant 800, the inflatablechannels 808 can be located near the proximal and distal ends 803, 804of the implant 800, preferably forming a configuration that approximatesa ring or toroid 807. These channels may be connected by intermediatechannels designed to serve any combination of three functions: (i)provide support to the tissue excluded by the implant 800, (ii) provideaxial and radial strength and stiffness to the 800, and/or (iii) toprovide support for the valve 104. The specific design characteristicsor orientation of the inflatable structure 813 can be optimized tobetter serve each function. For example if an inflatable channel 808were designed to add axial strength to the relevant section of thedevice, the channels 808 would ideally be oriented in a substantiallyaxial direction.

The cuff 802 and inflation channels 808 of the implant 800 can bemanufactured in a variety of ways. In one embodiment the cuff 802 ismanufactured from a fabric, similar to those fabrics typically used inendovascular grafts or for the cuffs of surgically implanted prostheticheart valves. The fabric is preferably woven into a tubular shape forsome portions of the cuff 802. The fabric may also be woven into sheets.In one embodiment, the yarn used to manufacture the fabric is preferablya twisted yarn, but monofilament or braided yarns may also be used. Theuseful range of yarn diameters is from approximately 0.0005 of an inchin diameter to approximately 0.005 of an inch in diameter. Depending onhow tight the weave is made. Preferably, the fabric is woven withbetween about 50 and about 500 yarns per inch. In one embodiment, afabric tube is woven with a 18 mm diameter with 200 yarns per inch orpicks per inch. Each yarn is made of 20 filaments of a PET material. Thefinal thickness of this woven fabric tube is 0.005 inches for the singlewall of the tube. Depending on the desired profile of the implant 800and the desired permeability of the fabric to blood or other fluidsdifferent weaves may be used. Any biocompatible material may be used tomake the yarn, some embodiments include nylon and PET. Other materialsor other combinations of materials are possible, including Teflon,fluoropolymers, polyimide, metals such as stainless steel, titanium,Nitinol, other shape memory alloys, alloys comprised primarily of acombinations of cobalt, chromium, nickel, and molybdenum. Fibers may beadded to the yarn to increases strength or radiopacity, or to deliver apharmaceutical agent. The fabric tube may also be manufactured by abraiding process.

The fabric can be stitched, sutured, sealed, melted, glued or bondedtogether to form the desired shape of the implant 800. The preferredmethod for attaching portions of the fabric together is stitching. Thepreferred embodiment uses a polypropylene monofilament suture material,with a diameter of approximately 0.005 of an inch. The suture materialmay range from about 0.001 to about 0.010 inches in diameter. Largersuture materials may be used at higher stress locations such as wherethe valve commissures attach to the cuff. The suture material may be ofany acceptable implant grade material. Preferably a biocompatible suturematerial is used such as polypropylene. Nylon and polyethylene are alsocommonly used suture materials. Other materials or other combinations ofmaterials are possible, including Teflon, fluoropolymers, polyimides,metals such as stainless steel, titanium, Kevlar, Nitinol, other shapememory alloys, alloys comprised primarily of a combinations of cobalt,chromium, nickel, and molybdenum such as MP35N. Preferably the suturesare a monofilament design. Multi strand braided or twisted suturematerials also may be used. Many suture and stitching patterns arepossible and have been described in various texts. The preferredstitching method is using some type of lock stitch, of a design suchthat if the suture breaks in a portion of its length the entire runninglength of the suture will resist unraveling. And the suture will stillgenerally perform its function of holding the layers of fabric together.

In some embodiments, the implant 800 is not provided with separateballoons, instead the fabric of the cuff 802 itself can form theinflation channels 808. For example, in one embodiment two fabric tubesof a diameter similar to the desired final diameter of the implant 800are place coaxial to each other. The two fabric tubes are stitched,fused, glued or otherwise coupled together in a pattern of channels 808that is suitable for creating the geometry of the inflatable structure813. In some embodiments, the fabric tubes are sewn together in apattern so that the proximal and distal ends of the fabric tubes form anannular ring or toroid 807. In some embodiments, the middle section ofthe implant 800 contains one or more inflation channels shaped in astep-function pattern. In some embodiments, the fabric tubes are sewntogether at the middle section of the implant to form inflation channels808 that are perpendicular to the toroids 807 at the end sections of theimplant 800. Methods for fabricating the implant 800 have been describedin U.S. Patent Publication No. 2006/0088836 to Bishop et al.

In the illustrated embodiment of FIGS. 3A and 3B, the struts 806 arearranged such that there is no radial overlap with the distal andproximal rings 807 a, 807 b. That is, in the illustrated embodiment, thestruts 808 do not increase the radial thickness of the inflationstructure because there is no radial overlap between the distal andproximal rings and the channels so that the channels lie within theradial thickness envelop defined by the distal and proximal rings 807 a,807 b. In another embodiment, the struts 808 can be wider in the radialdirection than the distal and proximal rings 807 a, 807 b such that thedistal and proximal rings 807 a, 807 b lie within a radial thicknessenvelop defined by the struts 806.

In one embodiment, the valve 800 can be delivered through a deploymentcatheter with an 18 F or smaller outer diameter and when fully inflatedhas an effective orifice area of at least about 1.0 square cm; and inanother embodiment at least about 1.3 square cm and in anotherembodiment about 1.5 square cm. In one embodiment, the valve 800 has aminimum cross-sectional flow area of at least about 1.75 square cm.

Leaflet Subassembly

With reference back to the embodiments of FIG. 2A, the valve 104preferably is a tissue-type heart valve that includes a dimensionallystable, pre-aligned tissue leaflet subassembly. Pursuant to thisconstruction, an exemplary tissue valve 104 can include a plurality oftissue leaflets that are templated and attached together at their tipsto form a dimensionally stable and dimensionally consistent coaptingleaflet subassembly. Then, in what can be a single process, each of theleaflets of the subassembly can be aligned with and individually sewn tothe cuff 802, from the tip of one commissure uniformly, around theleaflet cusp perimeter, to the tip of an adjacent commissure. As aresult, the sewed sutures act like similarly aligned staples, all ofwhich equally take the loading force acting along the entire cusp ofeach of the pre-aligned, coapting leaflets. Once inflated, the cuff 802can support the commissures with the inflation media and its respectivepressure which will solidify and create a system similar to a stentstructure. The resulting implant 800 thereby formed can reduce stressand potential fatigue at the leaflet suture interface by distributingstress evenly over the entire leaflet cusp from commissure tocommissure. In some embodiments, the tissue valve is coupled to theinflatable cuff 802 by attaching to the fabric of the cuff only.

In one embodiment, the tissue leaflets are not coupled to each other butare instead individually attached to the cuff 802.

A number of additional advantages can result from the use of the implant800 and the cuff 802 construction utilized therein. For example, foreach key area of the cuff 802, the flexibility can be optimized orcustomized. If desired, the coapting tissue leaflet commissures can bemade more or less flexible to allow for more or less deflection torelieve stresses on the tissue at closing or to fine tune the operationof the valve. Similarly, the base radial stiffness of the overallimplant structure can be increased or decreased by pressure or inflationmedia to preserve the roundness and shape of the implant 800.

Attachment of the valve 104 to the cuff 802 can be completed in anynumber of conventional methods including sewing, ring or sleeveattachments, gluing, welding, interference fits, bonding throughmechanical devices and methods such as pinching between members. Anexample of these methods are described in Published Applications fromHuynh et al (Ser. No. 06/102944) or Lafrance et al (2003/0027332) orU.S. Pat. No. 6,409,759 to Peredo, which are hereby incorporated byreference herein. These methods are generally know and accepted in thevalve device industry. The valve, whether it is tissue, engineeredtissue, mechanical or polymer, may be attached before packaging or inthe hospital just before implantation. Some tissue valves are nativevalves such as pig, horse, cow or native human valves. Most of which aresuspended in a fixing solution such as Glutaraldehyde.

In some embodiments, heart valve prostheses can be constructed withflexible tissue leaflets or polymer leaflets. Prosthetic tissue heartvalves can be derived from, for example, porcine heart valves ormanufactured from other biological material, such as bovine or equinepericardium. Biological materials in prosthetic heart valves generallyhave profile and surface characteristics that provide laminar,nonturbulent blood flow. Therefore, intravascular clotting is lesslikely to occur than with mechanical heart valve prostheses.

Natural tissue valves can be derived from an animal species, typicallymammalian, such as human, bovine, porcine canine, seal or kangaroo.These tissues can be obtained from, for example, heart valves, aorticroots, aortic walls, aortic leaflets, pericardial tissue such aspericardial patches, bypass grafts, blood vessels, human umbilicaltissue and the like. These natural tissues are typically soft tissues,and generally include collagen containing material. The tissue can beliving tissue, decellularized tissue or recellularized tissue. Tissuecan be fixed by crosslinking. Fixation provides mechanicalstabilization, for example by preventing enzymatic degradation of thetissue. Glutaraldehyde or formaldehyde is typically used for fixation,but other fixatives can be used, such as other difunctional aldehydes,epoxides, genipin and derivatives thereof. Tissue can be used in eithercrosslinked or uncrosslinked form, depending on the type of tissue, useand other factors. Generally, if xenograft tissue is used, the tissue iscrosslinked and/or decellularized. Additional description of tissuevalves can be found in U.S. Patent Publication No. 2009/008836 to Bishopet al.

Inflation Media

The inflatable structure 813 can be inflated using any of a variety ofinflation media, depending upon the desired performance. In general, theinflation media can include a liquid such water or an aqueous basedsolution, a gas such as CO₂, or a hardenable media which may beintroduced into the inflation channels 808 at a first, relatively lowviscosity and converted to a second, relatively high viscosity.Viscosity enhancement may be accomplished through any of a variety ofknown UV initiated or catalyst initiated polymerization reactions, orother chemical systems known in the art. The end point of the viscosityenhancing process may result in a hardness anywhere from a gel to arigid structure, depending upon the desired performance and durability.

Useful inflation media generally include those formed by the mixing ofmultiple components and that have a cure time ranging from a tens ofminutes to about one hour, preferably from about twenty minutes to aboutone hour. Such a material may be biocompatible, exhibit long-termstability (preferably on the order of at least ten years in vivo), poseas little an embolic risk as possible, and exhibit adequate mechanicalproperties, both pre and post-cure, suitable for service in the cuff invivo. For instance, such a material should have a relatively lowviscosity before solidification or curing to facilitate the cuff andchannel fill process. A desirable post-cure elastic modulus of such aninflation medium is from about 50 to about 400 psi—balancing the needfor the filled body to form an adequate seal in vivo while maintainingclinically relevant kink resistance of the cuff. The inflation mediaideally should be radiopaque, both acute and chronic, although this isnot absolutely necessary.

One preferred family of hardenable inflation media are two part epoxies.The first part is an epoxy resin blend comprising a first aromaticdiepoxy compound and a second aliphatic diepoxy compound. The firstaromatic diepoxy compound provides good mechanical and chemicalstability in an aqueous environment while being soluble in aqueoussolution when combined with suitable aliphatic epoxies. In someembodiments, the first aromatic diepoxy compound comprises at least oneN,N-diglycidylaniline group or segment. In some embodiments, the firstaromatic diepoxy compound are optionally substitutedN,N-diglycidylaniline. The substitutent may be glycidyloxy orN,N-diglycidylanilinyl-methyl. Non-limiting examples of the firstaromatic diepoxy compound are N,N-diglycidylaniline,N,N-diclycidyl-4-glycidyloxyaniline (DGO) and4,4′-methylene-bis(N,N-diglycidylaniline) (MBD), etc.

The second aliphatic diepoxy compound provides low viscosity and goodsolubility in an aqueous solution. In some embodiments, the secondaliphatic diepoxy compound may be 1,3-butadiene diepoxide, glycidylether or C₁₋₅ alkane diols of glycidyl ether. Non-limiting examples ofthe second aliphatic diepoxy compounds are 1,3-butadiene diepoxide,butanediol diglycidyl ether (BDGE), 1,2-ethanediol diglycidyl ether,glycidyl ether, etc.

In some embodiments, additional third compound may be added to the firstpart epoxy resin blend for improving mechanical properties and chemicalresistance. In some embodiments, the additional third compound may be anaromatic epoxy other than the one containing N,N-diglycidylanaline.However, the solubility of the epoxy resin blend can also decrease andthe viscosity can increase as the concentration of the additionalaromatic epoxies increases. The preferred third compound may betris(4-hydroxyphenyl)methane triglycidyl ether (THTGE), bisphenol Adiglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), orresorcinol diglycidyl ether (RDGE).

In some embodiments, the additional third compound may be acycloaliphatic epoxy compound, preferably more soluble than the firstaromatic diepoxy compound. It can increase the mechanical properties andchemical resistance to a lesser extent than the aromatic epoxy describedabove, but it will not decrease the solubility as much. Non-limitingexamples of such cycloaliphatic epoxy are 1,4-cyclohexanedimethanoldiclycidyl ether and cyclohexene oxide diglycidyl1,2-cyclohexanedicarboxylate. Similarly, in some embodiments, aliphaticepoxy with 3 or more glycidyl ether groups, such as polyglycidyl ether,may be added as the additional third compound for the same reason.Polyglycidyl ether may increase cross linking and thus enhance themechanical properties.

In general, the solubility of the epoxy resin blend decreases and theviscosity increases as the concentration of the first aromatic diepoxycompound increases. In addition, the mechanical properties and chemicalresistance may be reduced as the concentration of the aliphatic diepoxycompound goes up in the epoxy resin blend. By adjusting the ratio of thefirst aromatic dipoxy compound and the second aliphatic diepoxycompound, a person skilled in the art can control the desired propertiesof the epoxy resin blend and the hardened media. Adding the thirdcompound in some embodiments may allow further tailoring of the epoxyresin properties.

The second part of the hardenable inflation media comprises a hardenercomprising at least one cycloaliphatic amine. It provides goodcombination of reactivity, mechanical properties and chemicalresistance. The cycloaliphatic amine may include, but not limited to,isophorone diamine (IPDA), 1,3-bisaminocyclohexame (1,3-BAC), diaminocyclohexane (DACH), n-aminoethylpiperazine (AEP) orn-aminopropylpiperazine (APP).

In some embodiments, an aliphatic amine may be added into the secondpart to increase reaction rate, but may decrease mechanical propertiesand chemical resistance. The preferred aliphatic amine has thestructural formula (I):

wherein each R is independently selected from branched or linear chainsof C₂₋₅ alkyl, preferably C₂ alkyl. The term “alkyl” as used hereinrefers to a radical of a fully saturated hydrocarbon, including, but notlimited to, methyl, ethyl, n-propyl, isopropyl (or i-propyl), n-butyl,isobutyl, tert-butyl (or t-butyl), n-hexyl, and the like. For example,the term “alkyl” as used herein includes radicals of fully saturatedhydrocarbons defined by the following general formula C_(n)H_(2n+2). Insome embodiments, the aliphatic amine may include, but not limited to,tetraehtylenepentamine (TEPA), diethylene triamine and triethylenetetraamine. In some embodiments, the hardener may further comprise atleast one radio-opaque compound, such as iodo benzoic acids.

Additional details of hardenable inflation media are described inco-pending application titled “Inflation Media Formulation” ApplicationSer. No. 13/110,780, filed May 18, 2011, the entirety of which is herebyincorporated herein by reference. Other suitable inflation media arealso described in U.S. patent application Ser. No. 09/496,231 to Hubbellet al., filed Feb. 1, 2000, entitled “Biomaterials Formed byNucleophilic Addition Reaction to Conjugated Unsaturated Groups” andU.S. Pat. No. 6,958,212 to Hubbell et al. The entireties of each ofthese patents are hereby incorporated herein by reference.

Below is listed one particular two-component medium. This mediumcomprises:

First Part—Epoxy Resin Blend

(1) N,N-Diglycidyl-4-glycidyloxyaniline (DGO), present in a proportionranging from about 10 to about 70 weight percent; specifically in aproportion of about 50 weight percent,

(2) Butanediol diglycidyl ether (BDGE) present in a proportion rangingfrom about 30 to about 75 weight percent; specifically in a proportionof about 50 weight percent, and optionally

(3) 1,4-Cyclohexanedimethanol diglycidyl ether, present in a proportionranging from about 0 to about 50 weight percent.

Second Part—Amine Hardener

(1) Isophorone diamine (IPDA), present in a proportion ranging fromabout 75 to about 100 weight percent, and optionally

(2) Diethylene triamine (DETA), present in a proportion ranging fromabout 0 to about 25 weight percent.

The mixed uncured inflation media preferably has a viscosity less than2000 cps. In one embodiment the epoxy based inflation media has aviscosity of 100-200 cps. In another embodiment the inflation media hasa viscosity less than 1000 cps. In some embodiments, the epoxy mixturehas an initial viscosity of less than about 50 cps, or less than about30 cps after mixing. In some embodiments, the average viscosity duringthe first 10 minutes following mixing the two components of theinflation media is about 50 cps to about 60 cps. The low viscosityensures that the inflation media can be delivered through the inflationlumen of a deployment catheter with small diameter, such as an 18 Frenchcatheter

In some embodiments, the balloon or inflation channel may be connectedto the catheter on both ends. This allows the balloon to be pre-inflatedwith a non-solidifying material such as a gas or liquid. If a gas ischosen, CO₂ or helium are the likely choices; these gasses are used toinflate intra-aortic balloon pumps. Preferably the pre-inflation mediais radio-opaque so that the balloon position can be determined byangiography. Contrast media typically used in interventional cardiologycould be used to add sufficient radio-opacity to most liquidpre-inflation media. When it is desired to make the implant permanentand exchange the pre-inflation media for the permanent inflation media,the permanent inflation media is injected into the inflation channelthrough a first catheter connection. In some embodiments, the permanentinflation media is capable of solidifying into a semi-solid, gel orsolid state. As the permanent inflation media is introduced into theinflatable structure, the pre-inflation media is expelled out from asecond catheter connection. The catheter connections are positioned insuch a way that substantially all of the pre-inflation media is expelledas the permanent inflation media is introduced. In one embodiment anintermediate inflation media is used to prevent entrapment ofpre-inflation media in the permanent inflation media. In one embodimentthe intermediate inflation media is a gas and the pre-inflation media isa liquid. In another embodiment the intermediate inflation media orpre-inflation media functions as a primer to aid the permanent inflationmedia to bond to the inner surface of the inflation channel. In anotherembodiment the pre-inflation media or the intermediate inflation mediaserves as a release agent to prevent the permanent inflation media frombonding to the inner surface of the inflation channel.

The permanent inflation media may have a different radiopacity than thepre-inflation media. A device that is excessively radiopaque tends toobscure other nearby features under angiography. During thepre-inflation step it may be desirable to visualize the inflationchannel clearly, so a very radiopaque inflation media may be chosen.After the device is inflated with the permanent inflation media a lessradiopaque inflation media may be preferred. The feature of lesserradiopacity is beneficial for visualization of proper valve function ascontrast media is injected into the ventricle or the aorta.

Low Crossing Profile Delivery System

FIGS. 5A-5B illustrate an embodiment of a low crossing profile deliverycatheter 900 that can be used to deliver the implant 800. In general,the delivery system comprises a delivery catheter 900, and the deliverycatheter 900 can comprise an elongate, flexible catheter body having aproximal end and a distal end. In some embodiments, the catheter bodyhas a maximum outer diameter of about 18 French or less particularly atthe distal portion of the catheter body (i.e. the deployment portion).In some embodiments, the delivery catheter also comprises acardiovascular prosthetic implant 800 (e.g., configured as describedabove) at the distal end of the catheter body. While using acardiovascular prosthetic implant 800 as described above has certainadvantages, in modified embodiments, certain features of the deliverycatheter and delivery system described herein can also be used with aprosthetic implant that utilizes a stent or other support structureand/or does not utilize an inflation media.

As described herein, certain features of the implant 800 and deliverycatheter 900 are particularly advantageous for facilitating deliveringof cardiovascular prosthetic implant 800 within a catheter body havingouter diameter of about 18 French or less while still maintaining atissue valve thickness equal to or greater than about 0.011 inchesand/or having an effective orifice area equal to or greater than about 1cm squared, or in another embodiment, 1.3 cm squared or in anotherembodiment 1.5 cm squared. In such embodiments, the implant 800 can alsohave an expanded maximum diameter that is greater than or equal to about22 mm. In some embodiments, at least one link exists between thecatheter body and the implant 800. In some embodiments, the at least onelink is the PFL tubing. In one embodiment, the delivery system iscompatible with 0.035″ or 0.038″ guidewire.

In general, the delivery catheter 900 can be constructed with extrudedtubing using well known techniques in the industry. In some embodiments,the catheter 900 can incorporates braided or coiled wires and or ribbonsinto the tubing for providing stiffness and rotational torqueability.Stiffening wires may number between 1 and 64. In some embodiments, abraided configuration is used that comprises between 8 and 32 wires orribbon. If wires are used in other embodiments, the diameter can rangefrom about 0.0005 inches to about 0.0070 inches. If a ribbon is used,the thickness is preferably less than the width, and ribbon thicknessesmay range from about 0.0005 inches to about 0.0070 inches while thewidths may range from about 0.0010 inches to about 0.0100 inches. Inanother embodiment, a coil is used as a stiffening member. The coil cancomprise between 1 and 8 wires or ribbons that are wrapped around thecircumference of the tube and embedded into the tube. The wires may bewound so that they are parallel to one another and in the curved planeof the surface of the tube, or multiple wires may be wrapped in opposingdirections in separate layers. The dimensions of the wires or ribbonsused for a coil can be similar to the dimensions used for a braid.

With reference to FIGS. 5A and 5B, the catheter 900 can comprise anouter tubular member 901 having a proximal end 902 and a distal end 903,and an inner tubular member 904 also having a proximal end 905 and adistal end 906. The inner tubular member 904 can extend generallythrough the outer tubular member 901, such that the proximal and distalends 902, 903 of the inner tubular member 904 extend generally past theproximal end 902 and distal end 903 of the outer tubular member 901. Thedistal end 903 of the outer tubular member 901 can comprise a sheathjacket 912 and a stem region 917 that extends proximally from the sheathjacket 912. In some embodiments, the sheath jacket 912 may compriseKYNAR tubing. The sheath jacket 912 can house the implant 800 in aretracted state for delivery to the implantation site. In someembodiments, the sheath jacket 912 is capable of transmitting at least aportion of light in the visible spectrum. This allows the orientation ofthe implant 800 to be visualized within the catheter 900. In someembodiments, an outer sheath marking band 913 may be located at thedistal end 903 of the outer tubular member 901.

In one embodiment, the sheath jacket 912 can have a larger outsidediameter than the adjacent or proximate region of the stem region 917 ofthe tubular member 901. In such embodiments, the sheath jacket 917 andthe stem region 917 can comprise separate tubular components that areattached or otherwise coupled to each other. In other embodiments, thetubular member 901 can be expanded to form the larger diameter sheathjacket 912 such that the stem region 917 and sheath jacket 912 areformed from a common tubular member. In another embodiment or incombination with the previous embodiments, the diameter of the stemregion 917 can be reduced.

The proximal end 905 of the inner tubular member 904 can be connected toa handle 907 for grasping and moving the inner tubular member 904 withrespect to the outer tubular member 901. The proximal end 902 of theouter tubular member 901 can be connected to an outer sheath handle 908for grasping and holding the outer tubular member 901 stationary withrespect to the inner tubular member 904. A hemostasis seal 909 can bepreferably provided between the inner and outer tubular members 901,904, and the hemostasis seal 909 can be disposed in outer sheath handle908. In some embodiments, the outer sheath handle 908 comprises a sideport valve 921, and the fluid can be passed into the outer tubularmember through it.

In general, the inner tubular member 904 comprises a multi-lumenhypotube (see FIG. 6). In some embodiments, a neck section 910 islocated at the proximal end 905 of the inner tubular member 904. Theneck section 910 may be made from stainless steel, Nitinol or anothersuitable material which can serve to provide additional strength formoving the inner tubular member 904 within the outer tubular member 901.In some embodiments, a marker band 911 is present at the distal end 906of the inner tubular member 904. The multi-lumen hypotube can have awall thickness between about 0.004 in and about 0.006 in. In oneembodiment, the wall thickness is about 0.0055 in, which providessufficient column strength and increases the bending load required tokink the hypotube. With reference to FIG. 6, the inner tubular member904 (i.e., multi-lumen hypotube in the illustrated embodiment) cancomprise at least four lumens. One of the lumens can accommodate theguidewire tubing 914, and each of the other lumens can accommodate apositioning-and-fill lumen (PFL) tubing 916. The guidewire tubing 914can be configured to receive a guidewire. The PFL tubing 916 can beconfigured to function both as a control wire for positioning theimplant 800 at the implantation cite, and as an inflation tube fordelivering a liquid, gas or inflation media to the implant 800. Inparticular, the tubing 916 can allow angular adjustment of the implant800. That is, the plane of the valve (defined generally perpendicular tothe longitudinal axis of the implant 800) can be adjusted with thetubing 916.

With reference to FIGS. 5A and 5B, in general, the guidewire tubing 914can be longer than and can extend throughout the length of the deliverycatheter 900. The proximal end of the guidewire tubing 914 can passthrough the inner sheath handle 907 for operator's control; the distalend of the guidewire tubing 914 can extend past the distal end 903 ofthe outer tubular member 901, and can be coupled to a guidewire tip 915.The guidewire tip 915 can close the distal end 903 of the outer tubularmember 901 (or the receptacle) and protect the retracted implant 800,for example, during the advancement of the delivery catheter. Theguidewire tip 915 can be distanced from the outer tubular member 901 byproximally retracting the outer tubular member 901 while holding theguidewire tubing 914 stationary. Alternatively, the guidewire tubing 914can be advanced while holding the outer tubular member 901 stationary.The guidewire tubing 914 can have an inner diameter of about 0.035inches to about 0.042 inches, so the catheter system is compatible withcommon 0.035″ or 0.038″ guidewires. In some embodiments, the guidewiretubing 914 may have an inner diameter of about 0.014 inches to about0.017 inches, so the catheter system is compatible with a 0.014″diameter guidewire. The guidewire tubing 914 can be made from alubricious material such as Teflon, polypropylene or a polymerimpregnated with Teflon. It can also be coated with a lubricous orhydrophilic coating.

The guidewire tip 915 may be cone shaped, bullet shaped or hemisphericalon the front end. The largest diameter of the guidewire tip 915 ispreferably approximately the same as the distal portion 903 of the outertubular member 901. The guidewire tip 915 preferably steps down to adiameter slightly smaller than the inside diameter of the outer sheathjacket 912, so that the tip can engage the outer sheath jacket 912 andprovide a smooth transition. In the illustrated embodiment, theguidewire tip 915 is connected to the guidewire tube 914, and theguidewire lumen passes through a portion of the guidewire tip 915. Theproximal side of the guidewire tip 915 also has a cone, bullet orhemispherical shape, so that the guidewire tip 915 can easily beretraced back across the deployed implant 800, and into the deploymentcatheter 900. The guidewire tip 915 can be manufactured from a rigidpolymer such as polycarbonate, or from a lower durometer material thatallows flexibility, such as silicone. Alternatively, the guidewire tip915 may be made from multiple materials with different durometers. Forexample, the portion of the guidewire tip 915 that engages the distalportion 903 of the outer tubular member 901 can be manufactured from arigid material, while the distal and or proximal ends of the guidewiretip 915 are manufactured from a lower durometer material.

As will be explained in detail below, in one embodiment, the guidewiretip 915 is configured (e.g., has a tapered shape) to for directinsertion into an access vessel over a guidewire. In this manner, theguidewire tip 915 and the jacket 912 can be used to directly dilate theaccess vessel to accommodate an introducer catheter positioned over thedelivery catheter.

Each PFL tubing 916 can extend throughout the length of the deliverycatheter 900. The proximal end of the PFL tubing 916 passes through thehandle 907, and has a luer lock 917 for connecting to fluid, gas orinflation media source. The distal end of the PFL tubing 916 extendspast the distal end 906 of the inner tubular member 904 through thehypotube lumen. With reference to FIG. 5C, in some embodiments, the PFLtubing 916 comprises a strain relief section 918 at the proximal endwhere the tubing 916 is connected to the luer lock 917, and the strainrelief section 918 serves to relieve the strain on the PFL tubing 916while being maneuvered by the operator. The distal end of the PFL tubing916 comprises a tip or needle 919 for connecting to the implant 800. Insome embodiments, the tip 919 may have a threaded section toward the endof the needle 919 (see FIG. 5C). In some embodiments, the PFL tubing 916may have PFL marker(s) 920 at the distal end and/or proximal end of thetubing 916 for identification.

The PFL tubing 916 can be designed to accommodate for the ease ofrotation in a tortuous anatomy. The tubing 916 may be constructed usingpolyimide braided tube, Nitinol hypotube, or stainless steel hypotube.In a preferred embodiment, the PFL tubing 916 is made from braidedpolyimide, which is made of polyimide liner braided with flat wires,encapsulated by another polyimide layer and jacketed with prebax andnylon outer layer. In some embodiments, a Nitinol sleeve can be added tothe proximal end of the PFL tubing 916 to improve torque transmission,kinks resistance and pushability. In some embodiments, the outsidesurface of the PFL tubing 916 and/or the inside surface of the lumens inthe multi-lumen hypotube can also be coated with a lubricious siliconecoating to reduce friction. In some embodiments, an inner liningmaterial such as Teflon can be used on the inside surface of the lumensin the multi-lumen hypotube to reduce friction and improve performancein tortuous curves. Additionally, slippery coatings such as DOW 360, MDXsilicone or a hydrophilic coating from BSI Corporation may be added toprovide another form of friction reducing elements. This can provide aprecision control of the PFL tubings 916 during positioning of theimplant 800. In some embodiments, the outside surface of the PFL tubing916 can be jacketed and reflowed with an additional nylon 12 or RelsanAESNO layer to ensure a smooth finished surface. In some embodiments,anti-thrombus coating can also be put on the outside surface of the PFLtubing 916 to reduce the risk of thrombus formation on the tubing.

In some embodiments, the outer diameter of the catheter 900 can measurebetween about 0.030 inches to about 0.200 inches with a wall thicknessof the outer tubular member 901 being about 0.005 inches to about 0.060inches. In certain embodiments, the outer diameter of the outer tubularmember 901 can be between about 0.215 and about 0.219 inches. In thisembodiment, the wall thickness of the outer tubular member 901 isbetween about 0.005 inches and about 0.030 inches. The overall length ofthe catheter 900 can range from about 80 centimeters to about 320centimeters. In certain embodiments, the working length of the outertubular member 901 (from the distal end of the sheath jacket 912 to thelocation where the tubular member 901 is connected to the outer sheathhandle 908) can be about 100 cm to about 120 cm. In some embodiments,the inner diameter of the sheath jacket 912 can be greater than or equalto about 0.218 inches, and the outer diameter of the sheath jacket 912is less than or equal to about 0.241 inches. In a preferred embodiment,the outer diameter of the sheath jacket portion 912 can be less than orequal to about 0.236 inches or 18 French. In some embodiments, the outerdiameter of the PFL tubing 916 can be less than or equal to about 0.0435inches, and the length is about 140 cm to about 160 cm.

In the embodiments that employ a low crossing profile outer tubularmember, a low profile inflatable implant in a retracted state ispreferable for fitting into the sheath jacket 912. The sheath jacket 912can have an outer diameter of 18 French or less. In some embodiments,the implant 800 comprises a tissue valve 104 with an expanded outerdiameter greater than or equal to about 22 mm and a tissue thickness ofgreater than or equal to about 0.011 inches. The compressed diameter ofthe implant 800 may be less than or equal to about 6 mm or 18 French.The retracted implant 800 is generally loaded between the distal portion903 of the outer tubular member 901 and the distal portion 906 of theinner tubular member 904. The distal portion 903 of the outer tubularmember 901 therefore can form a receptacle for the implant 800. Theimplant 800 can be exposed or pushed out of the receptacle by holdingthe implant 800 stationary as the outer tubular member 901 is retracted.Alternatively, the outer tubular member 901 can be held stationary whilethe inner tubular member 904 is advanced and thereby pushing the implant800 out of the receptacle.

The delivery system can include a loading tool base 925 that can connectto the PFL tubing 916. In some embodiments, the PFL tubing 916 canconnect to the loading tool base 921 via a luer connection. Withreference to FIG. 7, one end of the loading tool base 921 can beconfigured to have step edge 923 s. In some embodiments, the distal endof the loading tool base has three step edges 923, each step edge 923has a luer connector 924 for connecting the PFL tubing 916. In someembodiments, the loading tool base 921 can also comprise at least twoadditional connectors 922 (e.g. additional luer connectors), each influid communication with one of the luer connector 924 on the steppededges 923, which would allow the introduction of fluid, gas or air intothe implant 800 for testing purposes. For example, in the exemplifiedembodiment, once the PFL tubings 916 are connected to the loading toolbase 921, a liquid or air source can be connected to the loading toolbase 921 via the additional connectors 922. The liquid or air can thenbe introduced into the implant 800 through the loading tool base 921 andthe PFL tubings 916.

The step edges 923 on the loading tool base 921 can allow the implant800 to be collapsed or folded up tightly so it can be loaded into thesheath jacket 912 at the distal end of the outer tubular member 901.When the proximal end of the PFL tubings 916 are connected to theloading tool base 921 and the distal end connected to the connectionports 809 of the implant 800, the step edge connections can pull the PFLtubings 916 in a way that creates an offset of the inflation valves 810and/or the connection ports 809 in the inflation channels 808 when theimplant 800 is folded or collapsed. By staggering the connectionports/inflation valves, the collapsed implant 800 can have a reducedcross-sectional profile. In some embodiments, the check valve 814 in theinflation channel is also staggered with the connection ports/inflationvalves in the collapsed state. Accordingly, in one embodiment, theinflation valves 810 and/or the connection ports 809 are axially alignedwhen the valve is positioned within the deployment catheter in acollapsed configuration. That is, the inflation valves 810 and/or theconnection ports 809 and/or check valve 814 are positioned such thatthey do not overlap with each other but are instead aligned generallywith respect to the longitudinal axis of the deployment catheter. Inthis manner, the implant 800 can be collapsed into a smaller diameter asopposed to a configuration in which with the inflation valves 810 and/orthe connection ports 809 and/or check valve 814 overlap each other in aradial direction, which can increase the diameter of the compressedimplant 800. In a similar manner, the channels 806 can be arrangedpositioned such hat they also do not overlap with each other. Theloading tool base 925 can be used to pull one end of the distal andproximal rings 807 a, 807 b in a proximal direction so as to align theinflation valves 810 and/or the connection ports 809 and/or check valve814 axially as described above and/or align the channels so as to reducethe overlap between multiple channels 806.

Combined Delivery System with Delivery Catheter and Introducer Catheter

FIG. 8A illustrates an exemplary embodiment of a combined deliverysystem 1000 that can be used to deliver an implant 800, such as theimplant embodiments described above. The combined delivery system 1000can include an introducer catheter 1030 and that is positioned at leastpartially over the delivery catheter 900 described above. As will beexplained in more detail below, in certain arrangements, it isadvantageous to use the combined delivery system 1000 because theintroducer catheter 1030 can have a smaller diameter than would possibleif the introducer catheter 1030 and the delivery catheter 900 areseparately introduced into the patient. For example, in the illustratedembodiment, the sheath jacket 912 of the delivery catheter 900 can havean outer diameter that is too large to be inserted through theintroducer catheter 1030 (i.e., the outer diameter of the sheath jacket912 can be larger than the inner diameter of the introducer catheter1030 and in some embodiments the outer diameter of the sheath jacket 912can be the same or substantially the same as the outer diameter of theintroduce catheter). Accordingly, by preassembling or building theintroducer catheter 1030 over a proximal portion of the deliverycatheter 900, a reduced diameter combined delivery system 1000 can becreated. In one embodiment, the introducer catheter 1030 is a 16 Frenchintroducer catheter capable of receiving a 16 French catheter. The outerdiameter the sheath jacket 912 of the delivery catheter 900 and a distalend of the introducer catheter 1030 can be about 18 French or smaller.It is believed that such a combined delivery system 1000 has a smallerouter diameter than any known approved delivery system and introducersystems for transcatheter heart valves. The smaller delivery system sizecan reduce vascular complications such as aortic dissection, access siteor access related vascular and/or distal embolization from a vascularsource particularly in situations in which the patient's femoral arteryhas a smaller diameter.

FIG. 9 illustrates the introducer catheter 1030 of the illustratedembodiment in more detail. In general, the introducer catheter 1030 cancomprise an elongate catheter having a proximal end 1032 and a distalend 1034. In some embodiments, the distal end 1034 of the introducercatheter 1030 can be tapered. The introducer catheter 1030 can comprisea seal assembly 1042 positioned at the proximal end 1032 of theintroducer catheter 1030.

An inner diameter of the introducer catheter 1030 can be smaller than anouter diameter of a distal portion of the delivery catheter 900. In someembodiments, the inner diameter of the introducer catheter 1030 is about16 French or less. In some embodiments, the introducer catheter 1030 cancomprise a commercially available introducer catheter having anappropriate diameter. For example, in some embodiments, the introducercatheter 1030 is a 16 F introducer catheter commercially available fromCook Medical®.

The seal assembly 1042 (see FIG. 10B) can threadably engage the proximalend 1032 of the introducer catheter 1030. The seal assembly 1042 caninclude a seal member 1046 configured to form a seal around the deliverycatheter 900. The seal assembly 1042 can be adjusted to maintain theposition of the introducer catheter 1030 relative to the deliverycatheter 900 during the procedure. In some embodiments, the sealassembly 1042 comprises a hemostasis seal/valve configured to minimizeblood loss during percutaneous procedures. In some embodiments, the sealassembly 1042 comprises a flush port 1044.

As discussed above, in general, the combined delivery system 1000comprises the delivery catheter 900, which extends through theintroducer catheter 1030. In the illustrated embodiment, the componentsof the delivery catheter 900 can be the same, similar, or identical tothe corresponding components of the low crossing profile deliverycatheter 900 discussed above accordingly. Accordingly, for the sake ofbrevity only certain components of the delivery catheter 900 will bedescribed below.

As noted above, the delivery catheter 900 can include outer tubularmember 901 having a proximal end 902 and a distal end 903, and an innertubular member 904 also having a proximal end 905 and a distal end 906.The inner tubular member 904 extends generally through the outer tubularmember 901, such that the proximal and distal ends 902, 903 of the innertubular member 904 extend generally past the proximal end 902 and distalend 903 of the outer tubular member 901. In some embodiments, thedelivery catheter 900 extends generally through the introducer catheter1030, such that the proximal end 902 and the distal end 903 of thedelivery catheter 900 extend generally past the proximal end 1032 andthe distal end 1034 of the introducer catheter 1030.

In several embodiments, the outer diameter of the distal portion of thedelivery catheter 900 and in particular, the sheath jacket 912, islarger than an inner diameter at the distal end of the introducercatheter 1030. In some embodiments, the outer diameter of the deliverycatheter 900 is about 18 French or less, particularly at the distalportion of the delivery catheter 900. In some embodiments, the outerdiameter at the proximal portion of the delivery catheter 900 is about16 French or less. In FIGS. 8A and 8B, the outer diameter of the sheathjacket 912, the proximal portion of the guidewire tip 915 and theintroducer catheter 1030 are illustrated as having different outerdiameters. However, in certain arrangements, the outer diameters ofthese components 912, 915 and 1030 can be the same or substantially thesame and the outer tubular member 901 can have a smaller outer diameterthan these components. In certain arrangements, the sheath jacket 912and the proximal portion of the guidewire tip 915 can have the sameouter diameter or substantially same outer diameter as the proximalportions of the introducer catheter 1030.

FIG. 10 illustrates a closer view of the outer tubular member 901. Thedistal end 903 of the outer tubular member 901 can form the sheathjacket 912. As noted above, the sheath jacket 912 can house the implant800 in a retracted state for delivery to the implantation site. In someembodiments, an outer diameter of the sheath jacket 912 is larger thanan outer diameter of stem portion 917 of the outer tubular member 901.In the illustrated embodiment, the outer diameter of the sheath jacket912 is larger than the inner diameter of at the distal end of theintroducer catheter 1030 while the stem portion 912 has an outerdiameter that is smaller than the inner diameter of the introducercatheter 1030. In some embodiments, the outer diameter of the sheathjacket 912 is about 18 F or less. In some embodiments, the outerdiameter of the stem portion 917 of the outer tubular member 901 is 16 For less. As described above, in some embodiments, the sheath jacket 912is a separate component connected to the step portion 917 of the outertubular member 901, while in other embodiments, the sheath jacket 912 isintegrally formed with the proximal of the outer tubular member 901.

As explained above, in some arrangements, it can be advantageous to usethe combined delivery system 1000 to reduce the diameter of theintroducer catheter 1030 used to deliver the delivery catheter 900 to atreatment site. If the introducer catheter 1030 and delivery catheter900 are separately introduced, the inner diameter of the introducercatheter 1030 has to be greater than the outer diameter of the largestportion of the delivery catheter 900 to be introduced into the patient.In contrast, in several embodiments of the combined delivery system1000, the outer diameter of the distal portion of the delivery catheter900 is greater than the inner diameter of the introducer catheter 1030.For example, in some embodiments, the outer diameter of the distalportion of the delivery catheter 900 is about 18 French, and the outerdiameter of the proximal portion of the delivery catheter 900 is about16 French. In some embodiments, the inner diameter of the introducercatheter 1030 is about 16 French. In some embodiments, the introducercatheter 1030 can be pre-installed over the proximal portion of thedelivery catheter 900.

Method of Deployment Using the Combined Delivery System

In several embodiments, an implant 800 may be deployed in an aorticposition using the combined delivery system 1000 described above and aminimally invasive procedure. In some embodiments, the method generallycomprises gaining access to the aorta, most often through the femoralartery. The vascular access site can be prepared according to standardpractice, and the guidewire can be inserted into the left ventriclethrough the vascular access.

As shown in FIG. 8A and as described above, the introducer catheter 1030can be pre-installed over the delivery catheter 900 prior to performingthe minimally invasive procedure. For example, the manufacturer canpre-install the introducer catheter 1030 over the delivery catheter 900.In some embodiments, the manufacturer extends the delivery catheter 900through the introducer catheter 1030 prior to completing assembly of thecombined delivery system 1000. For example, in some arrangements, it canbe desirable to extend the delivery catheter 900 through the introducercatheter 1030 prior to attaching a handle to the proximal end 902 ofouter tubular member 901. In other arrangements, it can be desirable toextend the delivery catheter 900 through the introducer catheter priorto attaching the sheath jacket 912 or implant 800 to the distal end 940of the delivery catheter 900.

In other embodiments, the operator (e.g., a nurse, physician, or otherindividual) extends the delivery catheter 900 through the introducercatheter 1030 prior to inserting the introducer catheter 1030 ordelivery catheter 900 into the patient. In some embodiments, the handleof the outer tubular member 901 can be removable, thus allowing the userto remove the handle and extend the delivery catheter 900 through theintroducer catheter 1030 prior to inserting the introducer catheter 1030or delivery catheter 900 into the patient.

In some embodiments, after the manufacturer or operator extends thedelivery catheter 900 through the introducer catheter 1030, a distalportion of the delivery catheter 900 extends distally from the distalend 1034 of the introducer catheter 1030. In some embodiments, thedistal sheath jacket 912 or implant 800 extends distally from the distalend 1034 of the introducer catheter 1030.

After the combined delivery system 1000 is assembled, as shown in FIG.10, the combined delivery system 1000 carrying the cardiovascularprosthetic implant 800 can be translumenally advanced. In someembodiments, the combined delivery system 1000 is inserted over theguidewire. In such embodiments, the guidewire tip 915 can be inserteddirectly into the access vessel over the guidewire such that theguidewire tip dilates the access vessel for the introducer catheter1030. In some embodiments, the combined delivery system 1000 is advanceduntil the seal assembly 1042 reaches the patient. In other embodiments,the introducer catheter 1030 is held in place while the deliverycatheter 900 is further advanced as shown in FIG. 8B. The deliverycatheter 900 can be advanced to a position proximate a native valve. Inother embodiments, the entire combined delivery system 1000, includingboth the introducer catheter 1030 and the delivery catheter 900 can beadvanced to a position proximate a native valve.

After the delivery catheter 900 is advanced over the aortic arch andpast the aortic valve, the position of the outer tubular member 901relative to the introducer catheter 1030 can be maintained by adjustingthe seal assembly 1042 to form a seal around the outer tubular member901.

As shown in FIG. 8C, in some embodiments, the implant 800 can berevealed or exposed by retracting the outer tubular member 901 partiallyor completely while holding the inner tubular member 904 stationary andallowing proper placement at or beneath the native valve. In someembodiments, the implant can also be revealed by pushing the innertubular member 904 distally while holding the outer tubular member 901stationary. Once the implant 800 is unsheathed, it may be movedproximally or distally, and the fluid or inflation media may beintroduced to the cuff 802 providing shape and structural integrity. Insome embodiments, the distal toroid of the inflatable cuff or inflatablestructure is inflated first with a first liquid, and the implant 800 ispositioned at the implantation cite using the links between the implant800 and the combined delivery system 1000. In some embodiments, no morethan three links are present. In some embodiments, the links are PRLtubes 916, which can be used to both control the implant 800 and to fillthe inflatable cuff. The implant 800 may be otherwise inflated orcontrolled using any of the other methods disclosed above.

In some embodiments, the links are PRL tubes 916, which can be used toboth control the implant 800 and to fill the inflatable cuff.

The deployment of the implant 800 can be controlled by the PFL tubes 916that are detachably coupled to the implant 800. The PFL tubes 916 areattached to the cuff 802 of the implant 800 so that the implant 800 canbe controlled and positioned after it is removed from the sheath ordelivery catheter 900. Preferably, three PFL tubes 916 are used, whichcan provide precise control of the implant 800 PFL tubes 916 duringdeployment and positioning. The PFL tubes 916 can be used to move theimplant 800 proximally and distally, or to tilt the implant 800 andchange its angle relative to the native anatomy.

In some embodiments, the implant 800 contains multiple inflation valves810 to allow the operator to inflate specific areas of the implant 800with different amounts of a first fluid or a first gas. With referenceto FIGS. 11A-C, in some embodiments, the implant 800 is initiallydeployed partially in the ventricle 32 (FIG. 11A). The inflation channel808 is filled partially, allowing the distal portion of the implant 800to open to approximately its full diameter. The implant is then pulledback into position at or near the native valve 34 annulus (FIG. 11B). Insome embodiments, the distal toroid 807 b is at least partially inflatedfirst, and the cardiovascular prosthetic implant 800 is then retractedproximally for positioning the cuff across the native valve 34. Thedistal ring 807 b seats on the ventricular side of the aortic annulus,and the implant 800 itself is placed just above the native valve 34annulus in the aortic root. At this time, the PFL tubes 916 may act tohelp separate fused commissures by the same mechanism a cutting ballooncan crack fibrous or calcified lesions. Additional inflation fluid orgas may be added to inflate the implant 800 fully, such that the implant800 extends across the native valve annulus extending slightly to eitherside (See FIG. 11C). The PFL tubes 916 provide a mechanism for forcetransmission between the handle of the deployment catheter 900 and theimplant 800. By moving all of the PFL tubes 916 together or the innertubular member 904, the implant 800 can be advanced or retracted in aproximal or distal direction. By advancing only a portion of the PFLtubes 916 relative to the other PFL tubes 916, the angle or orientationof the implant 800 can be adjusted relative to the native anatomy.Radiopaque markers on the implant 800 or on the PFL tubes 916, or theradio-opacity of the PFL tubes 916 themselves, can help to indicate theorientation of the implant 800 as the operator positions and orients theimplant 800.

In some embodiments, the implant 800 has two inflation valves 810 ateach end of the inflation channel 808 and a check valve 811 in theinflation channel 808. The check valve 811 is positioned so the fluid orgas can flow in the direction from the proximal toroid 807 a to thedistal toroid 807 b. In some embodiments, the implant 800 is fullyinflated by pressurizing the endoflator attached to the first PFL tube916 that is in communication with the first inflation valve 810 thatleads to the proximal toroid 807 a, while the endoflator attached to thesecond inflation valve 810 that is in communication with the distaltoroid 807 b is closed. The fluid or gas can flow into the distal toroid807 b through the one-way check valve. The proximal toroid 807 a is thendeflated by de-pressurizing the endoflator attached to the secondinflation valve. The distal toroid 807 b will remain inflated becausethe fluid or gas cannot escape through the check valve 811. The implant800 can then be positioned across the native annulus. Once in thesatisfactory placement, the proximal toroid 807 a can then be inflatedagain.

In some embodiments, the implant 800 may only have one inflation valve.When the inflation channel 808 is inflated with the first fluid or gas,the proximal portion of the implant 800 may be slightly restricted bythe spacing among the PFL tubes 916 while the distal portion expandsmore fully. In general, the amount that the PFL tubes 916 restricts thediameter of the proximal end of the implant 800 depends on the length ofthe PFL tubes 916 extend past the outer tubular member 901, which can beadjusted by the operator. In other embodiments, burst discs or flowrestrictors are used to control the inflation of the proximal portion ofthe implant 800.

The implant 800 can also be deflated or partially deflated for furtheradjustment after the initial deployment. As shown in FIG. 12A, theimplant 800 can be partially deployed and the PFL tubes 916 used to seatthe implant 800 against the native aortic valve 34. The implant 800 canthen be fully deployed as in shown in FIG. 12B and then tested as shownin FIG. 13C. If justified by the test, the implant 800 can be deflatedand moved as shown in FIG. 12D to a more optimum position. The implant800 can then be fully deployed and released from the control wires asshown in FIG. 12E.

As discussed above, in some embodiments, the first inflation fluid orgas can be displaced by an inflation media that can harden to form amore permanent support structure in vivo. Once the operator is satisfiedwith the position of the implant 800, the PFL tubes 916 are thendisconnected, and the catheter is withdrawn leaving the implant 800behind (see FIG. 12C), along with the hardenable inflation media. Theinflation media is allowed to solidify within the inflatable cuff. Thedisconnection method may included cutting the attachments, rotatingscrews, withdrawing or shearing pins, mechanically decouplinginterlocked components, electrically separating a fuse joint, removing atrapped cylinder from a tube, fracturing a engineered zone, removing acolleting mechanism to expose a mechanical joint or many othertechniques known in the industry. In modified embodiments, these stepsmay be reversed or their order modified if desired.

In some arrangements, it may be desirable to deliver a cardiovascularprosthetic implant 800 using a combined delivery system 1000 to reducethe number of components and steps necessary to position thecardiovascular prosthetic implant 800. For example, if the introducercatheter is inserted separately from the delivery catheter, the operatoruses a dilator to facilitate delivery of the introducer catheter. Insome scenarios, the dilator includes a flexible, elongate catheter bodyand a generally cone-shaped tip. The dilator is often a separatecomponent that extends through the introducer catheter and must beremoved after the introducer catheter is delivered to the appropriateposition. After the dilator is removed, the operator inserts thedelivery catheter through the introducer catheter. It can beadvantageous to eliminate the use of the dilator or eliminate thecatheter exchange step by delivering the cardiovascular prostheticimplant 800 using a combined delivery system 1000. Instead of relying onthe separate dilator component, the combined delivery system 1000 canuse the guidewire tip 915 to function as the dilator. As describedabove, in some embodiments, the guidewire tip 915 can be cone-shaped,bullet-shaped, or hemispherical-shaped to facilitate dilation. Further,the diameter of the guidewire tip 915 can be configured to form a smoothtransition from the distal end of the sheath jacket 912 to the guidewiretip 915. The smooth transition can help prevent the distal end of theintroducer catheter 1030 from damaging a vessel wall.

In certain arrangements, it is advantageous to deliver a cardiovascularprosthetic implant 800 using a combined delivery system 1000 to reducethe number steps necessary to remove the combined delivery system 1000after the implant 800 is delivered to the appropriate location. Forexample, if the introducer catheter is inserted separately from thedelivery catheter, the delivery catheter can be completely removed fromthe patient before the introducer catheter is removed from the patient.In some scenarios, it can be desirable to remove both the introducercatheter and delivery catheter simultaneously using the combineddelivery system 1000. After the implant 800 is delivered to theappropriate location, the PFL tubing 916 can be retracted proximallyinto the inner tubular member 904. In some embodiments, the deliverycatheter 900 is retracted proximally until a proximal end of the sheathjacket 912 abuts the distal end 1034 of the introducer catheter 1030.The guidewire tubing 914 can be retracted proximally until the guidewiretip 915 closes the distal end of the outer tubular member 901 and formsa smooth transition from the distal end 1034 of the introducer catheter1030 to the guidewire tip 915. The smooth transition can help preventthe distal end 1034 of the introducer catheter 1030 from damaging theblood vessel as the introducer catheter is removed from the patient. Theintroducer catheter 1030 and the delivery catheter 900 can then beremoved from the patient simultaneously.

With the integral introducer, it is desirable to have a relatively longtapered tip to facilitate introduction through tortuous arteries andtensioning of the sutures for arterial closure upon device removal, butfor safe deployment in the relatively small ventricle it is desirable tohave a tip that does not take up too much space. Several embodimentsaddressing this issue are described. These embodiments can be used incombination with the various embodiments described above.

In a first embodiment shown in FIG. 13, the distal portion of thecatheter tip 927 can be about 2 to 8 cm, similar to a dilator introducerfor a similarly sized introducer, but is extremely flexible, so that itcan follow the curve of the guidewire 914 inside the ventricle (seee.g., FIG. 14). In one embodiment the tip is manufactured from amaterial such as silicone or urethane with a durometer of less thanabout 25 A. In another embodiment the outer surface of the tip 927 issubstantially continuous but material from the internal volume of thetip is omitted allowing the tip to flex. Preferably the tip 927 iscapable of bending to a radius of less than 3 cm with less than 1 lbforce. More preferably the tip 927 is capable of bending to a radius ofless than 3 cm with less than 0.5 lb force. In another embodiment thetip 927 has a preset curve with a radius of approximately 2 to 8 cm ormore preferably about 3 to 5 cm. Preferably the curved tip 927 issubstantially straightened when placed over the stiff section of a verystiff 0.035 guidewire 914, and returns to a curved shape over theflexible or curved distal section of the guidewire 914. Preferably thetip 927 is radiopaque. This can be accomplished by filling the tip 927with a radiopaque material such as barium sulfate, tungsten or tantalum.

In another embodiment the device has a long tip in one configuration anda short tip in a second configuration, where the long tip is greaterthan about 3 cm and the short tip is less than about 3 cm. In a similarembodiment the long tip is greater than about 2 cm and the short tip isless than about 2 cm. The device is advanced through the iliac arteriesin the long tip configuration and advanced near the treatment locationinto the ventricle in the short tip configuration. In one embodiment along tip fits over a short tip and is held in place by at least onetension member which extends to a proximal portion of the device. Afterthe device has passed through the challenging access site the tensionmembers are loosened allowing the long tip to move away form the shorttip, but containing it for later removal.

In another embodiment the tip has a straight configuration and a bentconfiguration and can be oriented from one configuration to the other bydevices of a mechanism such as a pullwire.

In another embodiment the tip is inflatable, achieving a longconfiguration when pressurized and a short configuration when deflated,or when a vacuum is applied.

When treating a patient with the integral introducer sheath it istypically to introduce the device with the guidewire already in positionacross the aortic valve. In some cases this can present a challenge orrisk to keep the guidewire in proper position during device insertion.The embodiments describe herein include several methods to facilitatecrossing the native valve with the guidewire after the device isinserted

In one embodiment the guidewire exits the distal tip of the guidewire atan angle at least 5 degrees from the axis of the delivery system, andpreferably between 10 and 40 degrees. This allows the delivery catheterto be rotated to point the guidewire directly at the aortic valve toallow easy crossing of the valve with the guidewire. In one embodimentthe shape of the tip is similar to the shape of a coronary guidecatheter commonly used to cross the aortic valve.

In another embodiment the tip is deflectable and the bend of the tip canbe selected by the operator. In one embodiment this is accomplished byuse of a pull wire.

One embodiment includes a steerable guidewire as an accessory. Steerableguidewires are commonly known in the art.

In another embodiment a lumen is provided with a bend near the distalend and an outside diameter of approximately 0.035 or configured so thatit passes through the guidewire lumen. The inside diameter of the lumenis configured so that a 0.032, 0.018 or 0.014 or 0.009 guidewire canpass through it. This additional lumen can be used to control theguidewire and facilitate crossing the aortic valve with the guidewire.

When treating a patient with the integral introducer sheath it istypically necessary to introduce the device with the guidewire alreadyin position across the aortic valve. In some cases this can present achallenge or risk to keep the guidewire in proper position during deviceinsertion. The embodiments described herein include several methods tominimize the difficulty and risk of the sheath exchange.

In one embodiment the guidewire lumen exits the catheter at least 5, 1020 or 50 cm distal to the proximal end of the catheter. This allows asingle operator to control the guidewire position during the removal ofthe smaller sheath and the insertion of the device.

In one embodiment the guidewire passes through a lumen in the tip, whereone end of the lumen is at approximately the distal end of the tip andthe second end of the lumen is near a side of the tip distal to wherethe tip is in contact with the sheath portion of the delivery catheter.This provides the benefits of single operator guidewire control whileadditionally allowing the connection to the tip to be of smaller crosssectional area, allowing for further profile reduction.

When treating a patient with the integral introducer sheath it may bedesirable to have a larger diameter sheath for certain manipulationsthat are not used in all procedures, such as retrieval of the implant.In some embodiments the introducer can expand in these situations butmaintains the low profile of the device during normal use. Theexpandable introducer may be of a design similar to the e-sheathmarketed by Edwards Lifesciences or of a design similar to one marketedby onset medical. In another embodiment the introducer sheath can bemade from a polymer in a tubular cross section that expands duringretrieval through elastic and plastic deformation. The expandedconfiguration is preferably at least 10 percent larger than the nonexpanded configuration. The ID of the expanded configuration ispreferably similar to the OD of the non expanded configuration. The IDof the expanded configuration is preferably larger than the OD of thenon expanded configuration.

For the withdrawal of the device with the integral sheath, especiallywhen used with percutaneous closure techniques utilizing device such asprostar or proglide marketed by Abbot laboratories, it is preferable tobe able to tighten the sutures on the tapered tip of the device as thedevice is being removed from the patient. To facilitate easy removal thepreferred embodiments have a mechanism to lock the tip to the catheterbody and or the catheter body to the introducer sheath, so that bypulling back on a single component while cinching the sutures is asimple procedure requiring a minimum of coordination between multipleoperators.

In one embodiment the tip and the largest diameter portion of the outersheath are collapsible to facilitate their removal through an integralintroducer that is not substantially expandable. In one embodiment thecomponents are mechanically collapsible such that by providing axialforce to pull the components into the introducer sheath they collapse.In one embodiment the tip is made from nylon 12 with a hollow crosssection and a wall thickness of between 0.005 and 0.050 in.

In one embodiment the lock mechanism is a cam located in the proximalhandle that locks the guidewire lumen to the catheter body,substantially preventing relative motion between the catheter body andthe tip. In another embodiment a lock mechanism is a toughy-borst typevalve located on the proximal end of the integral introducer sheath thatcan be tightened to prevent relative motion between the integralintroducer sheath and the catheter body.

For the withdrawal of the device with the integral sheath, especiallywhen used with percutaneous closure techniques utilizing device such asprostar or proglide marketed by Abbot laboratories, it is important toknow the relative location of the tip, the distal and proximal ends ofthe large diameter portion of the delivery device and the distal portionof the integral introducer sheath.

One embodiment of the device includes radiopaque markers at thelocations described above. In another embodiment a visible mark on theouter portion of the delivery device that when aligned with a visiblemark or edge of the bub of the integral introducer, indicates that theproximal end of the large diameter portion of the delivery device isaligned with the distal end of the delivery catheter.

One embodiment includes an accessory device for accessing difficultiliac anatomies. An inverted tip balloon is inserted though thecontralateral side, and advanced through the aortic bifurcation backinto the access vessel. The inverted tip allows the guidewire to beadvanced through the device, and then through the guidewire lumen of theinverted tip balloon. The balloon can be advanced close to the device sothat the tip of the device is inside the inverted tip of the balloon.the device can be advanced through severe calcification and tortuosityby inflating the balloon and advancing the system with the balloon. Theinverted tip balloon has an OD similar to the OD of the delivery system,preferably between 3 mm and 8 mm. The balloon has a rated burst pressurebetween 2 and 20 atmospheres and preferably a guidewire lumen ofapproximately 0.036 in diameter. The balloon preferably has lowcompliance to maintain the inverted tip shape at pressure and allowdilation of the vessel to the size needed for device delivery withoutcausing unnecessary trauma.

The above-describe methods generally describes an embodiment for thereplacement of the aortic valve. However, similar or modified methodscould be used to replace the pulmonary valve or the mitral or tricuspidvalves. For example, the pulmonary valve could be accessed through thevenous system, either through the femoral vein or the jugular vein. Themitral valve could be accessed through the venous system as describedabove and then trans-septaly accessing the left atrium from the rightatrium. Alternatively, the mitral valve could be accessed through thearterial system as described for the aortic valve, additionally thecatheter can be used to pass through the aortic valve and then back upto the mitral valve. Additional description of mitral valve andpulmonary valve replacement can be found in U.S. Patent Publication No.2009/0088836 to Bishop et al.

The various methods and techniques described above provide a number ofways to carry out the embodiments described herein. Of course, it is tobe understood that not necessarily all objectives or advantagesdescribed may be achieved in accordance with any particular embodimentdescribed herein. Thus, for example, those skilled in the art willrecognize that the methods may be performed in a manner that achieves oroptimizes one advantage or group of advantages as taught herein withoutnecessarily achieving other objectives or advantages as may be taught orsuggested herein.

Furthermore, the skilled artisan will recognize the interchangeabilityof various features from different embodiments disclosed herein.Similarly, the various features and steps discussed above, as well asother known equivalents for each such feature or step, can be mixed andmatched by one of ordinary skill in this art to perform methods inaccordance with principles described herein. Additionally, the methodswhich is described and illustrated herein is not limited to the exactsequence of acts described, nor is it necessarily limited to thepractice of all of the acts set forth. Other sequences of events oracts, or less than all of the events, or simultaneous occurrence of theevents, may be utilized in practicing the embodiments of the invention.

Although the invention has been disclosed in the context of certainembodiments and examples, it will be understood by those skilled in theart that the invention extends beyond the specifically disclosedembodiments to other alternative embodiments and/or uses and obviousmodifications and equivalents thereof. Accordingly, the invention is notintended to be limited by the specific disclosures of preferredembodiments herein

What is claimed is:
 1. A method of positioning a prosthetic implantwithin a heart, the method comprising: advancing together a deliverycatheter and an introducer catheter that is preassembled over thedelivery catheter into a patient's vascular system, the deliverycatheter comprising a prosthetic valve and a distal tip that can beinserted directly into the access vessel such that the distal tipdilates the access vessel for the introducer catheter, wherein duringadvancement, an outer diameter of a distal end of the delivery catheterbeing greater than an inner diameter of a distal end of the introducercatheter, the introducer catheter comprising a hemostasis valve assemblyat a proximal end of the introducer catheter; translumenally advancingthe prosthetic valve to a position proximate a native valve of theheart, the prosthetic valve being at least partially disposed within thedistal end of the delivery catheter during advancement of the introducercatheter; and deploying the prosthetic valve.
 2. The method of claim 1,wherein the step of advancing the introducer catheter preassembled overthe delivery catheter comprising the prosthetic valve into the patientsvascular system comprises advancing the introducer catheter and deliverycatheter over a guidewire.
 3. The method of claim 1, wherein the step ofadvancing the introducer catheter preassembled over the deliverycatheter comprising the prosthetic valve into the patient's vascularsystem comprises inserting the introducer catheter into a femoralartery.
 4. The method of claim 1, wherein the step of translumenallyadvancing the prosthetic valve to a position proximate the native valveof the heart comprises advancing the prosthetic valve through an aorta.5. The method of claim 1, wherein deploying the prosthetic valvecomprises inflating a portion of the prosthetic valve.
 6. The method ofclaim 1, wherein the distal end of the delivery catheter is inserteddirectly into an access vessel.
 7. The method of claim 1, furthercomprising removing the delivery catheter and introducer cathetertogether from the patient.
 8. The method of claim 1, wherein deployingthe prosthetic valve comprises retracting the delivery catheter toexpose the prosthetic valve.
 9. The method of claim 8, wherein deployingthe prosthetic valve comprises holding the prosthetic valve stationaryas the delivery catheter is retracted.
 10. The method of claim 1,wherein the delivery catheter comprises an outer tubular member and aninner tubular member extending through the outer tubular member.
 11. Themethod of claim 10, wherein deploying the prosthetic valve comprisesadvancing the inner tubular member to push the prosthetic valve out ofthe outer tubular member.
 12. The method of claim 11, wherein deployingthe prosthetic valve comprises holding the outer tubular memberstationary as the inner tubular member is advanced.
 13. The method ofclaim 1 further comprising adjusting an angular position of theprosthetic valve using control wires.
 14. The method of claim 13,further comprising releasing the prosthetic valve from the controlwires.
 15. The method of claim 13, further comprising delivering fluidthrough the control wires to inflate the prosthetic valve.
 16. Themethod of claim 1, wherein deploying the prosthetic valve comprises:partially deploying the prosthetic valve; adjusting an angular positionof the prosthetic valve; and fully deploying the prosthetic valve. 17.The method of claim 1, further comprising simultaneously removing theintroducer catheter and the delivery catheter.
 18. The method of claim1, wherein the distal end of the delivery catheter comprises a sheathjacket, the sheath jacket having an outer surface that defines an outerdiameter of the sheath jacket, the outer diameter of the sheath jacketbeing greater than the inner diameter of the introducer catheter at thedistal end of the introducer catheter.
 19. The method of claim 18,further comprising, after deploying the prosthetic valve, retracting thedelivery catheter until a proximal end of the sheath jacket abuts thedistal end of the introducer catheter.
 20. The method of claim 1,wherein the delivery catheter comprises an outer tubular member and aguidewire tubing extending through the outer tubular member, theguidewire tubing being coupled to the distal tip of the deliverycatheter, wherein during advancement, the distal tip closes a distal endof the outer tubular member.
 21. The method of claim 20, furthercomprising distancing the distal tip from the outer tubular member. 22.The method of claim 21, wherein distancing the distal tip comprisingretracting the outer tubular member while holding the guidewire tubingstationary.
 23. The method of claim 21, wherein distancing the distaltip comprising advancing the guidewire tubing while holding the outertubular member stationary.
 24. The method of claim 20, furthercomprising, after deploying the prosthetic valve, retracting theguidewire tubing until the distal tip closes the distal end of the outertubular member.